期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 7, 期 7, 页码 513-520出版社
OXFORD UNIV PRESS
DOI: 10.1002/sctm.17-0295
关键词
Hematopoiesis; Hematopoietic stem cell; Stem cells; Ionizing radiation; DNA mismatch repair; Mlh1
资金
- NASA [NNX14AC95G]
- Cytometry & Microscopy and Radiation Resources Shared Resources of the Case Comprehensive Cancer Center [P30CA043703]
- NASA [NNX14AC95G, 686069] Funding Source: Federal RePORTER
One of the major health concerns on long-duration space missions will be radiation exposure to the astronauts. Outside the earth's magnetosphere, astronauts will be exposed to galactic cosmic rays (GCR) and solar particle events that are principally composed of protons and He, Ca, O, Ne, Si, Ca, and Fe nuclei. Protons are by far the most common species, but the higher atomic number particles are thought to be more damaging to biological systems. Evaluation and amelioration of risks from GCR exposure will be important for deep space travel. The hematopoietic system is one of the most radiation-sensitive organ systems, and is highly dependent on functional DNA repair pathways for survival. Recent results from our group have demonstrated an acquired deficiency in mismatch repair (MMR) in human hematopoietic stem cells (HSCs) with age due to functional loss of the MLH1 protein, suggesting an additional risk to astronauts who may have significant numbers of MMR deficient HSCs at the time of space travel. In the present study, we investigated the effects gamma radiation, proton radiation, and Fe-56 radiation on HSC function in Mlh1(+/+) and Mlh1(-/-) marrow from mice in a variety of assays and have determined that while cosmic radiation is a major risk to the hematopoietic system, there is no dependence on MMR capacity.
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